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Since the inception of the modern era of psychopharmacology, psychotropics have been the mainstay of the care of psychiatric patients all over the world, irrespective of their cultural and ethnic backgrounds. Until recently, however, variations in treatment response across populations, including effectiveness, dosing strategies, and adverse-effect profiles, have received minimal attention.1,2

Psychopharmacological research in general and randomized controlled trials in particular have been conducted largely in North America and Western Europe and have rarely included persons of ethnic minority or cross-cultural backgrounds.3 This, in part, reflects the asymmetrical distribution of resources and the “Eurocentric” slant of the research establishment. Responsibility for such biases also lies in deeply rooted beliefs and assumptions that suggest that treatment responses are predominantly determined by biological mechanisms and that biological processes are universally applicable and thus color- and culture-free.

In contrast, there have been remarkable changes in the past 3 decades in the documentation of often substantial variations in drug responses across cultural and eth-nic groups and in the delineation of mechanisms responsible for the variations.4,5 These findings have profound clinical and theoretical import, and it is important that they not be simplistically interpreted. As is true with all social and biological phenomena (eg, height, weight, temperament, child-rearing practices), drug response characteristics are normally distributed so that between-group differences are always accompanied by overlaps at the individual level.

Remarkable interindividual and intracultural variations coexist with ethnic/cultural differences. That is, while the majority of members of a population group fall on one side of the distribution, and those of another group on the other side, there are always exceptions. Neglect of such overlaps may lead to overgeneralization of research findings, which, in turn, could contribute to cultural stereotyping and consequent stigmatization.

For example, there are substantive ethnic variations in haloperidol metabolism between Asians and whites.6 At the same time, equally extensive interindividual variations within each of the ethnic groups also have been seen, resulting in significant overlap between the 2 groups.

This article reviews the cultural and biological aspects of drug effects and the role of interindividual, cross-ethnic, and genetic variations as well as environmental factors on treatment response.

Cultural aspects of drug effects

For the purposes of clarity in discussion, materials and opinions included in this article are presented with concepts that are commonly regarded as dichotomous in nature, such as culture and biology, as well as the “instrumental” versus “symbolic” aspects of pharmacological responses. In reality, increasing evidence indicates that such divisions are artificial and potentially misleading. In many instances, culture and biology clearly interact with and influence each other, as do medications’ “instrumental” (biological, pharmacological) and “symbolic” (nonbiological) effects. For example, drug-induced sedation may be regarded by one patient as a positive sign that suggests that the medication is beginning to work. For another patient, it may be an alarming sign of symptomatic worsening or a harbinger of medication toxicity. Such interpretations, based on individual beliefs that have been shaped largely by cultural and personal backgrounds, serve to further influence subsequent treatment response.

Keeping these caveats in mind, one of the most important issues that should be emphasized in any pharmacotherapeutic endeavor is that, however defined, the power of the symbolic aspect of treatment response typically outweighs instrumental effects of medications. It is for this reason that double-blind, randomized controlled trials are indispensable for the evaluation of the effectiveness of any intervention. In most clinical trials, placebo effects are seen in 30% to 50% of participants. New drugs usually need to show an additional 10% to 20% efficacy over placebo response to be approved for marketing and clinical use.

Placebo effects are largely determined by the patient’s expectations and beliefs, which are not only responsible for most of the therapeutic effects of treatment but can also lead to significant adverse effects.

The power of placebo response, mediated via symbolic mechanisms, is generally believed to be the basis for the popularity and effectiveness of most indigenous healing practices and alternative-treatment approaches. Thus, even if their instrumental properties are minimal as generally assumed, they could still provide therapeutic benefits that are substantive and at times dramatic. Embedded in patients’ sociocultural milieus, and often congruent with their beliefs and views on health and illness, such healing practices foster hope and expectations of recovery, thereby maximizing placebo response. Contrary to general belief, placebo responses are often accompanied by physiological changes (eg, changes in blood pressure, neurohormonal levels, brain imaging characteristics) that are indistinguishable from those seen with active pharmacological agents.7

In contrast, contemporary biomedical practices typically focus exclusively on the instrumental aspects of pharmacological effects. By downplaying or minimizing the symbolic aspect of medication effects and by regarding placebo responses as unreal and perhaps unworthy of scientific attention, clinicians can miss the opportunity to garner the power of the most important therapeutic element in patient care, which may not be easily compensated by their scientifically based professional knowledge and technical prowess.